Production of the protein VEGF-A, already known to stimulate the growth of blood vessels associated with tumors, also contributes in unexpected ways to the spread of cancer. In the April Journal of Experimental Medicine, researchers from Massachusetts General Hospital (MGH) and the Swiss Federal Institute of Technology describe finding that VEGF-A promotes the development of lymphatic vessels that can carry cancer cells to lymph nodes and can actually prepare the way for tumor metastasis by inducing new lymphatic vessels to grow within the nodes even before a secondary tumor has developed.

"This observation is our most surprising and exciting finding," says Michael Detmar, MD, of the MGH Cutaneous Biology Research Center, the study's senior author. "It's a new twist to the 'seed and soil' hypothesis, which postulates that distinct cancer types preferentially metastasize to organs that are optimally suited for them. Our results indicate that the 'seeds' can actively modify the 'soil' and prepare it for later metastatic arrival."

While it is now accepted that tumors can stimulate development of their own blood supply, a process called angiogenesis, similar growth of new lymphatic vessels was not suspected until 2001. At that time Detmar and his colleagues showed that human breast tumors implanted into mice induce the growth of lymphatic vessels and that lymphangiogenesis plays a key role in tumors' spread to lymph nodes. It had previously been believed that tumors had no functioning lymphatic vessels. The 2001 study focused on VEGF-C, the first factor identified to promote lymphatic vessel growth, and subsequent research has identified another lymphatic factor called VEGF-D, which also is active in the spread of cancer.

While VEGF-A had been believed to promote the development of new blood vessels only, recent research at the MGH and elsewhere found that it also induced proliferation of lymphatic tissue and vessels in laboratory and animal
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
4-Apr-2005

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